This invention relates to a process for introducing nitrile groups to compounds susceptible to Vilsmeier formylation. More specifically, a process is disclosed for introducing a nitrile group via two sequential reactions in a single reaction medium.
The formylation of aromatic and heterocyclic compounds by reaction with dialkylformamides or alkylarylformamides in the presence of phosphorus oxychloride is well known in the art. This reaction is commonly referred to as the Vilsmeier reaction.
It is also known that aldehydes can be converted to nitriles by reacting them with hydroxylamine hydrochloride in the presence of concentrated HCl or a dehydrating agent. J. March, Advanced Organic Chemistry, 2nd Ed., p. 827 (1977); Findlay et al, Can. J. Chem., 45, 1014 (1967) and VanEs, J. Chem. Soc., 1564 (1965). In general, this nucleophilic displacement reaction proceeds most readily in base.
There is no suggestion in the prior art that the conversion of an aldehyde to a nitrile using hydroxylamine hydrochloride would proceed readily in the presence of such a strong acidic dehydrating agent as phosphorus oxychloride. The skilled artisan would expect POCl.sub.3 to react rapidly and possibly explosively with the oxime intermediate produced by reaction between the hydroxylamine and aldehyde. Also the reaction between the hydroxylamine and aldehyde would be predicted to be very slow under such acidic conditions. Other undesirable reactions between the hydroxylamine and POCl.sub.3 might also be anticipated.
A convenient method of introducing nitrile groups to aromatic or heterocyclic compounds in a single reaction medium without isolation of intermediates would be desirable. The subject process is such a method.